Role of metal ions Nucleic acid tertiary structure

functional rnas folded, stable molecules three-dimensional shapes rather floppy, linear strands. cations essential thermodynamic stabilization of rna tertiary structures. metal cations bind rna can monovalent, divalent or trivalent. potassium (k) common monovalent ion binds rna. common divalent ion binds rna magnesium (mg). other ions including sodium (na), calcium (ca) , manganese (mn) have been found bind rna in vivo , in vitro. multivalent organic cations such spermidine or spermine found in cells , these make important contributions rna folding. trivalent ions such cobalt hexamine or lanthanide ions such terbium (tb) useful experimental tools studying metal binding rna.

a metal ion can interact rna in multiple ways. ion can associate diffusely rna backbone, shielding otherwise unfavorable electrostatic interactions. charge screening fulfilled monovalent ions. site-bound ions stabilize specific elements of rna tertiary structure. site-bound interactions can further subdivided 2 categories depending on whether water mediates metal binding. “outer sphere” interactions mediated water molecules surround metal ion. example, magnesium hexahydrate interacts , stabilizes specific rna tertiary structure motifs via interactions guanosine in major groove. conversely, “inner sphere” interactions directly mediated metal ion. rna folds in multiple stages , these steps can stabilized different types of cations. in stages, rna forms secondary structures stabilized through binding of monovalent cations, divalent cations , polyanionic amines in order neutralize polyanionic backbone. later stages of process involve formation of rna tertiary structure, stabilized largely through binding of divalent ions such magnesium possible contributions potassium binding.

metal-binding sites localized in deep , narrow major groove of rna duplex, coordinating hoogsteen edges of purines. in particular, metal cations stabilize sites of backbone twisting tight packing of phosphates results in region of dense negative charge. there several metal ion-binding motifs in rna duplexes have been identified in crystal structures. instance, in p4-p6 domain of tetrahymena thermophila group intron, several ion-binding sites consist of tandem g-u wobble pairs , tandem g-a mismatches, in divalent cations interact hoogsteen edge of guanosine via o6 , n7. ion-binding motif in tetrahymena group intron a-a platform motif, in consecutive adenosines in same strand of rna form non-canonical pseudobase pair. unlike tandem g-u motif, a-a platform motif binds preferentially monovalent cations. in many of these motifs, absence of monovalent or divalent cations results in either greater flexibility or loss of tertiary structure.

divalent metal ions, magnesium, have been found important structure of dna junctions such holliday junction intermediate in genetic recombination. magnesium ion shields negatively charged phosphate groups in junction , allows them positioned closer together, allowing stacked conformation rather unstacked conformation. magnesium vital in stabilizing these kinds of junctions in artificially designed structures used in dna nanotechnology, such double crossover motif.